Oxazole

Oxazole is the parent compound for a vast class of heterocyclic aromatic organic compounds. These are azoles with an oxygen and a nitrogen separated by one carbon. Oxazoles are aromatic compounds but less so than the thiazoles. Oxazole is a weak base; its conjugate acid has a p''K''_a of 0.8, compared to 7 for imidazole.

Preparation

Classical oxazole synthetic methods in organic chemistry are
* the Robinson–Gabriel synthesis by dehydration of 2-acylaminoketones
* the Fischer oxazole synthesis from cyanohydrins and aldehydes
* the Bredereck reaction with α-haloketones and formamide
* the Van Leusen reaction with aldehydes and TosMIC

Other methods:
* Oxazolines can also be obtained from cycloisomerization of certain propargyl amides. In one study oxazoles were prepared via a one-pot synthesis consisting of the condensation of propargyl amine and benzoyl chloride to the amide, followed by a Sonogashira coupling of the terminal alkyne end with another equivalent of benzoylchloride, and concluding with ''p''-toluenesulfonic acid catalyzed cycloisomerization:

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*In one reported oxazole synthesis the reactants are a nitro-substituted benzoyl chloride and an isonitrile:

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Biosynthesis

In biomolecules, oxazoles result from the cyclization and oxidation of serine or threonine nonribosomal peptides:

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Oxazoles are not as abundant in biomolecules as the related thiazoles with oxygen replaced by a sulfur atom.

Reactions

With a pK_a of 0.8 for the conjugate acid, oxazoles are far less basic than imidazoles (pK_a = 7).Thomas L. Gilchrist "Heterocyclic Chemistry" 3rd ed. Addison Wesley: Essex, England,
1997. 414 pp. .
* Deprotonation of oxazoles at C2 is often accompanied by ring-opening to the isonitrile.
* Electrophilic aromatic substitution takes place at C5 requiring activating groups.
* Nucleophilic aromatic substitution takes place with leaving groups at C2.
* Diels–Alder reactions with oxazole dienes can be followed by loss of oxygen to form pyridines.
* The Cornforth rearrangement of 4-acyloxazoles is a thermal rearrangement reaction with the organic acyl residue and the C5 substituent changing positions.
* Various oxidation reactions. One study"Ceric Ammonium Nitrate Promoted Oxidation of Oxazoles", David A. Evans, Pavel Nagorny, and Risheng Xu. ''Org. Lett.''; 2006; 8(24) pp 5669 - 5671; (Letter) reports on the oxidation of 4,5-diphenyloxazole with 3 equivalents of CAN to the corresponding imide and benzoic acid:
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: In the balanced half-reaction three equivalents of water are consumed for each equivalent of oxazoline, generating 4 protons and 4 electrons (the latter derived from Ce^IV).

See also

* Isoxazole, an analog with the nitrogen atom in position 2.
* Imidazole, an analog with the oxygen replaced by a nitrogen.
* Thiazole, an analog with the oxygen replaced by a sulfur.
* Benzoxazole, where the oxazole is fused to another aromatic ring.
* Pyrrole, an analog without the oxygen atom.
* Furan, an analog without the nitrogen atom.
* Oxazoline, which has one double bond reduced.
* Oxazolidine, which has both double bonds reduced.
* Oxadiazoles with two nitrogens instead of one (e.g. furazan).
* Oxazolone, an analog with a carbonyl group

References

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Simple aromatic rings